Dialkyl aryl sulfoxides

Optically active dialkyl sulfoxides of high optical purity (>95%), which could not be prepared from menthyl alkanesulfmates, have been synthesized by Johnson et al. (93) via reaction of chiral alkyl aryl sulfoxides with alkyllithium reagents. The exchange of the... 

The second approach to chiral aminosulfonium salts consists of the conversion of chiral sulfoxides into aminosulfonium salts by means of MA -diethylaminosulfinyl tetrafluoroborate (165). The reaction occurs with predominant retention of configuration at sulfur with dialkyl and alkyl aryl sulfoxides. However, its stereospecificity is strongly dependent on the nature of substituents in the starting sulfoxide. In the case of diaryl sulfoxides this method failed to give chiral aminodiarylsulfonium salts. 

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

All diaryl sulfoxides, some alkyl aryl sulfoxides (e.g., methyl p-tolyl sulfoxide, 41), and some dialkyl sulfoxides (e.g., methyl 1-adamantyl sulfoxide), were found to undergo racemization according to the pyramidal inversion mechanism. Mislow and co-workers (248) have found that for most of the compounds investigated, irrespective of the nature of the substituents attached to sulfur, the first-order rate constant for racemization in p-xylene at 210 C is about 3 X 10" sec", corresponding to a half-life of about 6 hr. Moreover, the activation parameters do not show significant differences and their values were contained in a narrow range 35 to 42 kcal/mol and... 

The activation parameters of the pyramidal inversion have been determined for various dialkyl, diaryl, and alkyl aryl sulfoxides. They vary between 35 and 42 keal/mol for AH, and -8 and +4 cal/(mol-K) for AS. These values indicate that, in most cases, the thermal stereomutation of sulfoxides occurs at a significant rate only at about 200 °C. There are a few exceptions, such as benzyl and allyl sulfoxides, whose racemization is raised at 130-150 and 50-70 °C, respectively. 

The main methodologies developed until now for enantioselective oxidation of sulfides are effective only in the oxidation of alkyl aryl sulfoxides. Dialkyl sulfoxides on the other hand are generally oxidized with only poor selectivity. In an attempt to solve this problem, Schenk s group69 recently reported a stereoselective oxidation of metal-coordinated thioethers with DMD. The prochiral thioether is first coordinated to a chiral ruthenium complex by reaction with the chloride complexes [CpRu[(S,S)-chiraphos]Cl], 36. Diastereoselective oxygen transfer from DMD produces the corresponding sulfoxides in high yield and selectivity. The chiral sulfoxides 37 are liberated from the complexes by treatment with sodium iodide. Several o.p. aryl methyl sulfoxides have been obtained by this method in moderate to high ee (Scheme 12). 

Snyder s modification of the Wudl method is suitable for the synthesis of dialkyl and alkyl aryl sulfoxides in high ee. Both enantiomeric sulfoxides may be produced, either by reversing the order of organometallic displacement or by using the (IS, 2/ )-(+)-enantiomer of ephedrine, which is commercially available. Compared with... 

The reactions between a-metalloalkyl sulfoxides and electrophiles have been extensively studied. Although alkylations of the sodium or potassium salts of dialkyl sulfoxides are not always very efficient since a,a -dialkylated sulfoxides are often produced (or stilbene in the case of methyl-sulfinyl carbanion and benzyl bromide ), those employing the lithioalkyl aryl sulfoxides work more efficiently with alkyl or allyl halides " and with epoxides. " " Typical examples of these alkylations, allylations and hydroxyalkylations (from epoxides) are illustrated in Scheme 86. 

Treatment of methyl phenyl sulfoxide with diethylaminosulfur trifluoride (DAST), in the presence of antimony trichloride provides 159 in quantitative yield (66). The reaction proceeds in good yield with dialkyl sulfoxides and alkyl aryl sulfoxides (163). Reoxidation of the a-fluorosulfide (165) to the corresponding sulfoxide (161), followed by pyrolysis, provides a direct synthesis of fluoroolefins (65). The reaction is believed to proceed by a Pummerer-type mechanism (l.e., a fluoro-Pummerer reaction, Scheme 48). Similarly, Umemoto (67) reported that N-fluorocollidine (167) converted sulfides to ot-fluorosulfides (170) presumably via an S-fluorosulfonium cation species 168 (Scheme 49). The synthetically challenging fluorovinyl ether nucleosides (175) and (176) were prepared using the fluoro-Pummerer reaction (Scheme 50) (60) the (E)-isomer (175) could be isomerized to 176 under photolytic conditions. Finch and co-workers (69) converted 160 to the sulfoximine 178 and demonstrated the utility of this compound as a mild fluoromethylene synthon (Scheme 51). Base-catalyzed condensation 178 with a carbonyl compound gave 179 which afforded... 

The photolysis imder direct and sensitized conditions of several simple dialkyl and alkyl aryl sulfoxides was reported by Shelton and Davis in 1973 [14]. Among these was phenyl tefr-butyl sulfoxide 78. We will not discuss the results with sensitizers at length here, because we believe the mechanism of sensitization is unclear and some reactions had decidedly different product distributions as a function of sensitizer. 

Johnson was able to overcome the synthetic limitations of the Andersen procedure by inducing the displacement of aryl groups from diaryl or alkyl aryl sulfoxides with either alkyllithium or alkyl sodium reagents as a general approach to optically active, unsymmetrical dialkyl sulfoxides (Scheme 2.4, Table 2.1) [13]. 

In conclusion, Snyder and Benson s approach allows the synthesis of enantiomerically pure dialkyl and alkyl aryl sulfoxides in good yields and with excellent enantioselectivities. Both enantiomers are accessible by reversing the order of organometallic displacement or by employing the (15,2J )-(+)-ephedrine enantiomer. The only limitations are observed in the synthesis of t-butyl phenyl and aryl phenyl sulfoxides. However aryl phenyl sulfoxides are accessible by the Andersen procedure, and t-butyl phenyl sulfoxides by an approach to chiral sulfoxides developed by Kagan, described below. 

The results for the preparation of dialkyl or alkyl aryl sulfoxides are shown in Table 2.13. 

Table 2.13 Preparation of dialkyl and alkyl aryl sulfoxides from cyclic sulfite (34) or (35)...

The S=0 stretching vibration in alkyl and aryl sulfoxides gives rise to strong absorption at 1065-1030 cm" The S=0 stretching vibration in dialkyl sulfites gives rise to strong absorption at 1220-1195 Alkyl... 

Miscellaneous Reactions. Bromodimethylborane can also be used to convert dialkyl, aryl alkyl, and diaryl sulfoxides to the corresponding sulfides (eq 15). Typically, the sulfoxides are treated with 2.5 equiv of Me2BBr in dichloromethane at —23 °C for 30 min and at 0°C for 10 min. Bromine is produced in the reaction and must be removed in order to avoid possible side reactions. This is accomplished by saturating the solution with propene prior to introducing the reagent or by adding cyclohexene. Phosphine oxides and sulfones failed to react under the conditions used to deoxygenate sulfoxides. 

Oae and coworkers oxidized several diaryl, dialkyl and alkyl aryl sulfides to their corresponding sulfoxides using purified cytochrome P-450 obtained from rabbit liver microsomes138. In agreement with expectations, this enzyme did not exhibit much stereospecificity. Some examples including the observed e.e. values are shown by 121-125. A model was proposed to account for the absolute configurations of the sulfoxides produced (126). The sulfur atom is preferentially oxidized from the direction indicated. 

In summary, the evidence described above demonstrates three main mechanistic features of the rearrangement of allylic sulfenates to sulfoxides (1) spontaneous and wholly concerted [2,3]-sigmatropic shift of allyl or a-substituted allyl esters (7 a, b) at one extreme (2) complete stability of the y-aryl and y,y-dialkyl substituted allyl sulfenates as well as... 

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

Enzymes, in particular peroxidases, catalyze efficiently the enantioselective oxidation of alkyl aryl sulfides and also dialkyl sulfides, provided that the alkyl substituents are sterically differentiable by the enzyme. The peroxidases HRP, CPO, MP-11, and the mutants of HRP, e. g. F41L and F4IT, were successfully used as biocatalysts for the asymmetric sulfoxidation (Eq. 14). A selection of sulfides. 

In combination with H2O2 (salen)Mn(III) complexes 173a, b, i-n have also been employed by Jacobsen and coworkers as catalysts for the asymmetric oxidation of sulfides to sulfoxides, without a need for additives. From the structurally and electronically different Mn-salen catalysts screened, 173i turned out to be the most active and selective one (equation 58) . While dialkyl sulfides underwenf uncafalyzed oxidation with H2O2, aryl alkyl sulfides were oxidized only slowly compared wifh fhe cafalyzed pathway. Using... 

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